Since the first penicillin compounds were used successfully to fight pathogenic organisms such as bacteria, several generations of new anti-infective agents have been developed. Some of these agents, such as ceftriaxone, streptomycin, gentamicin and cefazolin, are normally poorly absorbed through mucosal tissue into the bloodstream and are, therefore, of limited or no practical value when administered via any route other than parenteral to fight systemic bacterial infections. Administration of these difficult-to-absorb drugs is sometimes accomplished by infusion, but more typically by intravenous or intramuscular injections.
Some injectable antibiotics, such as ceftriaxone, can be administered once a day and are therefore more convenient to use. However, for the most part, injectable antibacterial drugs must be given more frequently than once daily to achieve greatest effectiveness, and such treatments often require the services of a doctor, nurse or trained technician on a continual basis. The experience of frequent injections can also be distressful or unnerving for some patients.
Efforts have been made to find materials which promote the absorption of antibiotics and other pharmaceuticals that normally are poorly absorbed through mucosal tissue, the objective being to enable the formulation of non-injectable dosage forms such as capsules, tablets, pills, suppositories, and so forth with such pharmaceuticals. Some substances, such as ionic surfactants, sodium lauryl sulfate and cnelating agents (e.g., EDTA) are known to be rather harmful to the mucosal membrane, although they have been reported to enhance the intestinal absorption of large molecules. On the other hand, as described in the patent literature, the enhanced rectal absorption of antibiotics is obtained by the use of promoters such as hydroxy aromatic acid salts, e.g., sodium salicylate and sodium homovanillate, U.S. Pat. No. 4,406,896 (Higuchi et al.); cholic acid, or its salt, together with a fatty acid glyceride (e.g. WITEPSOL, known in the trade as Witepsol H15) and a polyethylene alkyl ether, Japan patent publication No. 57158-719; cholic acid, or its salt, together with a fatty acid glyceride, Japan patent publication No. 5062-007; a fatty acid glyceride (e.g., Witepsol) together with a polyoxyethylene glycol (PEG)-fatty acid ester, U.S. Pat. No. 4,732,753 (Fuller); and a bile acid in combination with a polyoxyethylene-fatty acid ester and a glycerol-fatty acid ester, U.S. Pat. No. 4,156,719 (Sezaki).
The absorption promotion of orally delivered antibiotics with the use of a cholic acid salt or taurocholic acid salt is described by Miyamoto et al., in J. Pharm. Sci. 72. 651-654 (1983).
U.S. Pat. No. 4,525,339 (Behl et al.) discloses active oral dosage forms of beta-lactam antibiotics using C.sub.2 -C.sub.12 fatty acid mono-, di- or triglycerides as the absorption enhancer.
The permucosal absorption of various therapeutics, including antibiotics, is reported to be enhanced by the use of fatty acids and saturated or unsaturated fatty acid glycerides, in Swiss patent publication No. 634,749.